POS0925 HIGH LEVELS OF BOTH CCL2 AND CCL17 WERE ASSOCIATED WITH MORE SEVERE SSc-ILD
Authors: I. Barua, V. Palchevskiy, H. Fretheim, H. Didriksen, T. Garen, T. M. Aaløkken, S. S. Weigt, Ø. Molberg, J. Belperio, A. M. Hoffmann-Vold
Journal: Annals of the Rheumatic Diseases (2022)

Background Systemic sclerosis (SSc) carries a high risk for progressive interstitial lung disease (ILD). Several anti-inflammatory therapies have been used to treat SSc-ILD and recently the first antifibrotic therapy has been approved. Personalized treatment strategies are largely missing to date. The two chemokines, CCL2 (MCP-1) and CCL17 (TARC), have been shown to be markers of inflammation and fibrosis, respectively. Objectives To examine associations between ILD severity and serum levels of CCL2 and CCL17 in two different but complementary sources of biomaterial. Methods Sera from the prospective Oslo University Hospital SSc cohort (n=371) and healthy blood donor controls (HC; n=100) and lung tissue at the time of lung transplantation from UCLA SSc-ILD patients (n = 12) and healthy donors (n = 12) were analyzed for CCL2 and CCL17 by multiplex assays. CCL2 and CCL17 levels were defined in serum as high or low using 95% CI in HC sera as cut-off values. Paired pulmonary function tests and HRCT images were obtained at baseline and follow-up. ILD was diagnosed on HRCT and categorized by the extent of lung fibrosis as limited (&lt;10%) or extensive (&gt;10%) ILD. Cellular sources of CCL-2 and CCL-17 in lung tissues were determined by immunohistochemistry. Descriptive statistics were applied. Results CCL2 and CCL17 were increased in SSc in sera and in lung tissue compared to HC (Figure 1). High levels of CCL17 (&gt;700 pg/ml) and CCL2 (&gt;1000pg/ml) in sera were identified in 43/254 (17%) and 84/471(18%) of the SSc patients (Table 1 and Figure 1). High levels of both CCL17 and CCL2 were associated with lower FVC at baseline and higher extent of lung fibrosis on HRCT (Table 1). Of those with high CCL2 and CCL17, 67% had extensive lung fibrosis. Categorization of ILD into no ILD, limited or extensive ILD showed an association between high CCL17 levels and the extent of fibrosis (Table 1). Reactive epithelium and macrophages and plasma cells expressed TARC, while more AM and infiltrating mononuclear cells expressed CCL-2. Conclusion High levels of both CCL17 and CCL2 were associated with more severe ILD and expressed in end-stage kung tissue and may reflect an ongoing inflammatory and fibrotic processes in SSc-ILD. This may have an implication on treatment choices for SSc-ILD. Disclosure of Interests Imon Barua: None declared, Vyacheslav Palchevskiy: None declared, Håvard Fretheim Shareholder of: non-financial support from GSK and Actelion, outside the submitted work.,, Consultant of: Consultant of: Personal fees from Bayer and non-financial support from GSK and Actelion, outside the submitted work.,, Henriette Didriksen: None declared, Torhild Garen: None declared, Trond Mogens Aaløkken: None declared, Stephen Samuel Weigt: None declared, Øyvind Molberg: None declared, John Belperio: None declared, Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Jansen, Lilly, Medscape, Merck Sharp &amp; Dohme, Roche,, Consultant of: Actelion, ARXX therapeutics, Bayer, Janssen,, MSD, Lilly, Roche, Boehringer-Ingelheim, Medscape.,,, Grant/research support from: Boehringer Ingelheim